Studies are being designed to determine which of the major classes of hepatic cells are responsible for the uptake of different lipoproteins by the liver and to define which apoproteins mediate the uptake of lipoprotins by the different cell types. Rat endothelial, Kupffer and parenchymal cells have been isolated by collagenase liver perfusion, centrifugation on Percoll gradients and centrifugal elutriation. Apoproteins isolated from normal subjects and patients with Tangier disease were radioiodinated and reassociated with lipoprotein particles from normal subjects and patients with Tangier disease. Measurements of the uptake of these labeled particles by hepatic cells in vitro indicate that the increased reticuloendothelial (RE) cell uptake of cholesterol in Tangier disease is probably mediated by enhanced uptake of Tangier apoprotein A-I-containing cholesterol-rich lipoproteins by RE cells and that the rapid clearance of lipoproteins from the plasma in Tangier disease can be account for by the uptake of Tangier aproprotein A-I-containing lipoproteins by hepatocytes.